The cellular components of peripheral blood in the circulatory system of a human is comprised principally of red blood cells, i.e., erythrocytes, and white blood cells, i.e., leukocytes. The function of leukocytes and their clinical relevance has generated great interest in the scientific community. The family of leukocytes is comprised of neutrophils, monocytes, eosinophils, basophils and lymphocytes. Many of these cell types have numerous functional subsets.
Neutrophils, monocytes, eosinophils and basophils are known as phagocytes because their primary function in the human immune system is to phagocytose or ingest bacteria and other microorganisms. These cells originate in the bone marrow of a human. However, each of these phagocytes has different functions and behaves as a related but separate system. Although originating in the bone marrow, phagocytic cells do enter into and circulate in peripheral blood.
The general function of the phagocyte system is to achieve phagocytosis by immunological response to a foreign substance. Neutrophils are very efficient as a phagocyte for bacteria that have been coated with an antibody and not as efficient for bacteria without antibody coating. The major function of the neutrophil is to prevent invasion by pathogenic microorganisms by localizing and killing them.
Eosinophils function in the phagocyte system in a manner which is similar to that of neutrophils. In in vitro tests, the two leukocytes may respond to the same antigenic challenges. However, the response of eosinophils generally is not as efficient as neutrophils in terms of phagocytosis and killing bacteria. Recent studies have indicated that eosinophils are important in defense against chronic parasitic infections where neutrophils are not as effective.
The neutrophil is the most common cell in bone marrow and the most common leukocyte in peripheral blood. One microliter of a normal whole blood sample includes, on average, 5.times.10.sup.3 leukocytes of which 3,075 are neutrophils, 150 are eosinophils, 25 are basophils, 250 are monocytes and 1500 are lymphocytes. The departure from the normal concentration of neutrophils in peripheral blood has recognized clinical relevance. Thus, increased concentrations of neutrophils, sometimes termed "neutrophilia", may evidence certain disease or physical conditions, while decreased concentrations of neutrophils in peripheral blood, sometimes termed "neutropenia", would have different clinical relevance. In the case of eosinophils, an increase over the normal concentration of eosinophils in a blood sample is termed "eosinophilia"; a decrease in the normal concentration of eosinophils in a blood sample is termed "eosinopenia". Eosinophilia is associated with clinical conditions, such as allergic conditions, drug hypersensitivity reaction and leukemia-like illnesses. Eosinopenia, for instance, is sometimes associated with an ongoing inflammatory process.
Numerous monoclonal antibodies have been developed which bind specifically to neutrophils. Reinherz et al., Leukocyte Typing II: Volume 3, Human Mycloidance Hematopoietic Cells, Springer-Verlag, N.Y., 1986; Girardet et al. American Journal Cancer, Vol. 32, pp 177-183 (1983); Bernstein et al., the Journal of Immunology, Vol. 128, No. 2, pp. 876-881, (February), 1982; Skubitz et al., Blood, Vol 61, No. 1, pp. 19-26, (January), 1983; Majdic et al., Blood, Vol. 58, No. 6, pp. 1127-1133 (December), 1981. The monoclonal antibodies disclosed in these publications exhibit binding specificities for neutrophils, both mature and immature, but have not been shown to bind to a unique determinant site on both neutrophils and eosinophils.